This is a competitive continuation of an on going series of studies to test the efficacy and effectiveness of novel antipsychotic in neuroleptic treatment resistant schizophrenic patients. Support for this proposal will also continue support for a significant Public and Academic Liaison initiative the Treatment Research Unit of the University of Maryland at Baltimore. In our initial work, we have develop[ed a standard clinical protocol to test candidate drugs for differential effect in neuroleptic treatment resistant schizophrenic inpatients. The study proposed in this application will test the efficacy of sertindole, quetiapine, and risperidone versus fluphenazine in this population. The drugs will be tested in a drug-drug double-blind parallel group design. The study will last 24-weeks. Patients will be selected for poor neuroleptic response because of a history of a least one year of persistent symptoms, a history of failure to respond to at least two adequate trials of neuroleptics over the past five years and poor global functioning for the past five years. Patients who enter the trial will also have failed to respond to six seeks of prospective haloperidol therapy. The current drugs that will be studied, along with olanzapine, whose evaluation we are completing now, represent all of the new antipsychotic drug that will be available in the near future. Future candidate drugs will be selected based on the outcome of this trial and will be the subject of future submissions. This design provides substantial power for testing superiority of a candidate drug. Results will be analyzed with regard to improvement in total BPRS score and psychotic symptoms. We will also assess improvements to quality of life, living skills and dischargability. This study size is based on a predicted effect of 11% difference in total symptoms and a 22% difference in positive symptoms with a power of 0.80 and alpha of 0.05 (two-tailed).